Scientists move to quash threat of smallpox as terrorist's weapon

Scientists at the La Jolla Institute for Allergy & Immunology have made an advancement in research to combat the growing threat of bioterrorism.

Viral disease expert Shane Crotty led a team of institute scientists in identifying an antibody in humans that quickly fights the smallpox virus, thus protecting society against a potential smallpox outbreak. Crotty and his team discovered a protein in the smallpox virus, the H3 protein, that elicits a strong human antibody response. Findings were made by studying blood samples from people who received the smallpox vaccine.

"We've been working to identify antibodies people make to the smallpox vaccine that really do neutralize the virus," said Crotty. "That's what our recent discovery was about. We've shown that it can protect mice from dying. That's a pretty good indicator to us."

Mitchell Kronenberg, president of La Jolla Institute for Allergy & Immunology, hailed Crotty's work as an important scientific breakthrough. "We've known about vaccinating against smallpox since the 1700s," Kronenberg said, "but it's amazing how no one's ever studied in detail how the virus is recognized by the body's defense system. It turns out, your immune system doesn't see the whole virus, just a piece of it. Shane (Crotty) found one particular protein, the H3 protein, which seems to play probably the most important part in stimulating your immune system. What this means is, vaccines can be developed which don't require any virus at all, just the use of this protein. Potentially, you can make this protein which effectively neutralizes and inhibits the virus."

As a result of Crotty's team's discovery, the National Institutes of Health is now funding further research by them to better understand the molecular processes involved in smallpox antibody production.

Smallpox is an acute, highly contagious virus disease characterized by prolonged fever, vomiting and pustular eruptions that can kill as many as half of those affected who have not been immunized against it. "It's actually thought to have caused the most human deaths of any infectious disease over the past thousand years or so," Crotty said.

The smallpox virus was eradicated in the United States by 1950, and vaccinations against the disease for the general public were ended in 1972. But in the aftermath of 9-11, new concerns have arisen that the smallpox virus could be revived and used as a bioterror disease agent.

"What makes the smallpox virus

credible," said Crotty, "is that it's very easy to grow and make large amounts of, which makes it appealing as a biological war agent."

Crotty noted the former Soviet Union was involved in researching smallpox's potential as a biological weapon. It was hoped its stockpiles of smallpox virus were destroyed.

"But there's at least an outside chance that some bad people got a hold of some it," Crotty said. "That's what led to smallpox being at the top of the list of bioterrorism concerns for the United States. That led to groups, like mine, trying to reevaluate the disease and come up with solutions to it, just in case. That's where all this work came from."

Kronenberg added Crotty's discovery could eventually lead to high-quality batches of anti-H3 antibody being stockpiled around the world right alongside the supplies of smallpox vaccine.

"This could be very important should people become infected before they have a chance to be vaccinated," Kronenberg said.

The smallpox vaccine needs to be administered to people before they're exposed to the virus in order for it to work. There are a lot of people who can't be innoculated.

"The problem is," Crotty said, "there are people with weakened immune systems - pregnant women, the elderly - who shouldn't be vaccinated because there are side effects to a live viral vaccine, though it works real well in a small percentage of people."

What happens now, said Crotty, is that researchers like him are now working to design and make lots of smallpox antibody.

"This will be a stockpile thing," he said. "We want to have backups around in case the virus did show up. In fact, to some extent, it's even simply a deterrent. Don't do it because we can stop it."

La Jolla Institute for Allergy & Immunology is a nonprofit academic research institute that does basic scientific research in immunology.

"We are analogous to Salk or the Burnham Institute," Kronenberg said. "Our focus is on immunology and infectious diseases. We do a lot of research on this really beautiful, elegant, multi-faceted system that protects you from diseases, and how it works."